In Vivo Microbeam Radiation Therapy at a Conventional Small Animal Irradiator

CANCERS(2024)

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摘要
Simple Summary Microbeam radiation therapy (MRT) is a novel, still pre-clinical form of radiation therapy for cancer treatment, where the dose is applied in spatial fractions. MRT was shown to be able to treat tumors effectively while causing reduced damage to normal tissue. Research on MRT nowadays requires large, expensive, and difficult-to-access facilities. In this study, we aim to develop an easily accessible MRT setup utilizing a conventional small animal irradiator. We developed a comprehensive treatment planning system with a dose calculation accuracy of 10%. We successfully applied microbeam radiation to a mouse in vivo and showed that the microbeam pattern is preserved by analyzing histological sections of a mouse brain. We demonstrated the feasibility of MRT using our developed setup.Abstract Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against gamma H2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.
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关键词
microbeam radiation therapy,spatially fractionated radiation therapy,treatment planning,dose calculation,dosimetry,small animal irradiator,histology
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